Systemic and topical corticosteroid
treatment of oral lichen planus: a
M. Carbone
E. Goss
M. Carrozzo
S. Castellano
D. Conrotto
R. Broccoletti
S. Gandolfo
Department of Biomedical Sciences and
Human Oncology, Oral Medicine Section,
School of Medicine and Dentistry, University of
Turin, Italy
Correspondence to:
Dr Mario Carbone
Clinica Odontostomatologica,
C.so Dogliotti 14, 10126 Torino, Italy
e-mail: mario_carbone@libero.it
Accepted for publication January 30, 2003
Copyright Blackwell Munksgaard 2003
J Oral Pathol Med . ISSN 0904-2512
Printed in Denmark . All rights reserved
comparative study with long-term follow-up
Abstract
Background: Topical corticosteroids are the mainstay treatment
for oral lichen planus (OLP), but some authors suggest that
systemic corticosteroid therapy is the only way to control acute
presentation of OLP.
Methods: Forty-nine patients with histologically proven atrophic
erosive OLP were divided into two groups matched for age and
sex. The test group (26 patients) was treated systemically with
prednisone (50 mg/day), and afterwards with clobetasol oint-
ment in an adhesive medium plus antimicotics, whereas the
control group (23 patients) was only treated topically with clobe-
tasol plus antimycotics.
Results: Complete remission of signs was obtained in 68.2% of
the test group and 69.6% of the control group, respectively
(P 0.94). Similar results were obtained for symptoms. Follow-
up showed no signicant differences between the two groups.
One-third of the patients of the test group versus none in the
control group experienced systemic side-effects (P 0.003).
Conclusions: The most suitable corticosteroid therapy in the
management of OLP is the topical therapy, which is easier and
more cost-effective than the systemic therapy followed by topical
therapy.
Key words: oral lichen planus; systemic corticosteroids; therapy;
topical corticosteroids
J Oral Pathol Med 2003: 32: 3239
Oral lichen planus (OLP) is a relatively common chronic inam-
matory disease (1). Although often not presenting symptomatic
hyperkeratosic lesions, OLP may be painful especially in the
atrophic and erosive forms or where there is desquamative
gingivitis. A vast array of empirical treatments (1, 2) have been
reported, but several studies have lacked adequate controls.
Moreover, randomized control studies have been few, have
usually involved small populations, and most reports include
favourable responses to the studied treatment, suggesting pos-
sible publication bias (2, 3). Because of the heterogeneity of the
published reports, regarding both experimental design of trials
and criteria of response to therapy, many data cannot be directly
compared, and meta-analysis is impossible (2, 3). Curiously,
323
Carbone et al.
several suggested treatments are also suspected to induce
lichenoid lesions (1). One of the most important problems in
management of OLP is its chronic nature, which warrants long-
term therapy. Moreover, the patient's medical history (history of
diabetes, hypertension, liver disease), psychological state, treat-
ment compliance, and possible drug interactions must be
remembered when evaluating the cost-effectiveness of any treat-
ment.
A number of recent reviews on OLP therapy are available
(19), and most of them suggest that the best treatment remains
high-potency topical corticosteroids, whereas systemic corticos-
teroids may be occasionally indicated for severe recalcitrant
erosive OLP or for patients with diffuse mucocutaneous involve-
ment. Sixty-six to hundred percent of the topically steroid-treated
patients respond at least partially, with variation in efcacy mostly
as a result of the different potency of the corticosteroids (7).
Clobetasol propionate appears to be the most effective topical
steroid, as 5675% of the patients treated with it in adhesive base
underwent complete remission (58). Moreover, after 6 months
follow-up, 65% of the clobetasol-treated patients maintained the
improvement (5). Clobetasol propionate has also been used as a
mouthwash in aqueous solution, but this preparation may give
rise to adrenocortical hypofunction (9).Very recently, other topi-
cal corticosteroids, as uticasone propionate spray and beta-
methasone sodium phosphate in mouth rinses, have been
used, but they appear to be probably less effective than clobetasol
(10).
However, some authors suggest that the systemic corticoster-
oid therapy is often the only way to control acute presentation of
the disease (4), even if one study (11) suggests that the symptoms
of OLP are better controlled with topical corticosteroids than with
systemic corticosteroids or a combination of both. Unfortunately,
the study did not include any statistical comparison, and so
denite conclusions could not be drawn.
The aim of this study was to analyze the long-term efcacy and
safety of systemic plus topical corticosteroid therapy compared
with topical treatment alone, in the treatment of OLP.
Materials and methods
Patients
The trial involved 49 patients (36 women, 13 men, mean age
60.6  9.7 years; range 4081 years), with atrophicerosive
OLP, conrmed histologically (1). According to Scully et al.
324 J Oral Pathol Med 32: 3239
and Silverman et al. (1, 12), the clinical forms were characterized
by reticular keratosis plus erithematous changes and/or ulcera-
tions. After the medical history was recorded, the patients under-
went hepatic screening as published by Carrozzo et al. (13). The
subjects were excluded from the trial if they presented histologic
signs of dysplasia, had been taking drugs capable of inducing
lichenoid reactions, or had chronic liver disease. Patients were
divided successively into two groups matched for sex and age.
The test group, made up of 26 patients (20 women, 6 men, mean
age 62.4  8.7 years; range 4178 years) received systemic and
topical corticosteroids plus antimycotic treatment, whereas the
control group included 23 patients (16 women, 7 men, mean age
58.6  10.5 years; range 4081 years), and received only topical
corticosteroids plus antimycotic treatment. Blood pressure and
weight were assessed weekly during systemic treatment, and
were routinely obtained at follow-up visits from the patients
treated topically. Blood glucose level, serum electrolytes, blood
cortisol levels, serum creatinine and azotemia levels, and com-
plete blood counts were recorded at the start and at the end of the
treatment, according to the previously reported studies (5, 12, 14).
At each examination, any adverse effect or discomfort related to
the therapy were also documented. Informed consent was
obtained beforehand.
Treatment protocol
Patients of the test group were treated with prednisone (Delta-
cortene Forte1; Lepetit, Cormano, Milano, Italy) at 50 mg/day in
a single morning dose for variable lengths of time, anyhow not up
to 60 days. Because the median weight of the patients was 56 kg,
the above dose corresponded to a daily median dose of less than
1 mg/kg for every patient. When an almost 50% reduction in lesion
size was achieved, the prednisone dose was tapered to 25 mg/day
for 1 week, then to 12.5 mg/day for 1 week, and nally to 6 mg/
day for the last week. Topical corticosteroid therapy was then
begun using 0.05% clobetasol propionate ointment (Clobesol1;
Glaxo, Verona, Italy) mixed in equal parts with 4% hydroxyethyl
cellulose gel as previously reported (10). Clobetasol propionate
was initially applied twice daily, then once daily for a total period of
6 months. All patients received concomitant antimycotic treat-
ment against oropharyngeal candidiasis. This consisted of mico-
nazole gel (Micotef1, LPB, Cinisello B., Milano, Italy) applied
once daily, oral rinse with 0.12% chlorhexidine (Plak-Out1; BYK,
Gulden Italia, Cormano, Milano, Italy) (10).
The prednisone-treated patients were checked every week,
and the dose and length of the treatment were adjusted in each
case following the clinical needs. Patients of the control group
 Corticosteroid treatment of oral lichen planus

were instead treated with only 0.05% clobetasol propionate oint-
ment in adhesive medium plus antimycotic therapy as above.
Clobetasol propionate was applied twice daily for the rst
4 months and then once daily for the following 2 months.
Recording symptoms and follow-up
Statistical analysis
The Wilcoxon's rank-sum test was used for repeated measures on
the same individuals. Chi-square analysis with Yates correction or
Fisher's exact test were used to compare the responses between the
groups. P-values of <0.05 were considered statistically signicant.

After treatment, the patients were examined every 2 months in the

rst year, every 3 months in the second year, and every 6 months
after the third year of follow-up. The patients' clinical progress
was recorded at each visit on a computerized patient chart. The
chart showed a diagram of the oral cavity with color-coded areas
for hyperkeratosic, atrophic, or erosive lesions, to graphically
represent the course of the disease. The data were then scored
according to the scale used by Thongprasom et al. (15):
2
5: Erosive area >1 cm .
4: Erosive area <1 cm2.
2
3: Atrophic area >1 cm .
2: Atrophic area <1 cm2.
1: Presence of hyperkeratosic striae.
0: No lesions.
During visits, the patients were asked to evaluate their symp-
toms, which were then assigned a score:
3: Serious.
2: Average.
1: Mild.
0: None.
The difference between the baseline and endpoint scores
numerically expressed the progress in the clinical and the symp-
tomatologic improvement in each of the test groups. Complete
remission of the clinical signs was dened as the disapperance of
all the atrophicerosive lesions after 6 months of treatment with
only mild white striae or without striae. Scores were either 0 or 1.
Complete resolution of the symptoms was dened as the absence
of any discomfort corresponding to the 0 score. Partial remission
or persistence of the patient's condition meant a fall or no change
in the patient's score.
Results
The most often affected area of the mouth was the buccal mucosa
(85% of the patients), followed by the gingiva (53%), the tongue
(26%), the lips (14%), and the palate (18%). Cutaneous lesions of
lichen planus were present in 13.6% of the patients. Five patients
(10%) had mild hypertension. Of the 49 patients enrolled initially, 4
(8%) dropped out because of missed follow-up or incomplete
results. Results from the two groups are shown in Tables 13.
Comparison of the scores for signs and symptoms before and
after treatment was statistically signicant for both the groups
(Table 1). After 6 months of therapy, 68.2% of the patients in the
test group had complete remission, 22.7% showed partial remis-
sion (Figure 1), and 9.1% had no benecial response to the
treatment. In the control group, 69.6% had complete remission
(Figure 2), 26% showed partial remission, and 4.4% showed no
effect (Table 2). Similar results were found for symptoms (Table 3).
There were no signicant differences in improvement of both the
signs and the symptoms between the two groups (Tables 2 and 3).
Follow-up continued for an average of 36 months (range
14 years). Fifty percent of the patients in the test group did
not maintain the results obtained at the end of the treatment, with
an 8.9-month average period with no lesions, whereas 54.5% of the
patients of the control group did not maintain the results after an
average period without lesions of 7 months. Even in this case,
there were no signicant differences between the two groups
(P 0.81). Seven patients (31.8%) of the test group suffered

Table 1. Signs and symptoms scores before and after systemic plus topical and only topical therapies

Clinical response

Signs score Symptoms score

Test (n 22) Controly (n 23) Test (n 22) Control (n 23)
Before treatment 4.68  0.5z 4.91  0.29 2.5  1.3 2.2  1.2
After treatment 2.91  0.3 3  0.0 0.41  0.6 0.8  0.9
P <0.0001 <0.0001 <0.0001 <0.0001

Treated with prednisone plus clobetasol.
yTreated with clobetasol.
zMean  SD.

J Oral Pathol Med 32: 3239 325

Carbone et al.

Table 2. Comparison of signs among patients with oral lichen planus (OLP) treated with systemic plus topical and topical therapy after 2 and 6 months
of treatment

Clinical response

After 2 months of treatment After 6 months of treatment

Group Complete response Partial response No response Complete response Partial response No response

Test (n 22) 9 (40.9%) 11 (50%) 2 (9.1%) 15 (68.2%) 5 (22.7%) 2 (9.1%)
Controly (n 23) 8 (34.8%) 14 (60.8%) 1 (4.4%) 16 (69.6%) 6 (26%) 1 (4.4%)
P 0.90z 0.66z 0.60 0.82z 0.93z 0.60

Treated with prednisone plus clobetasol.
yTreated with clobetasol.
zChi-square with Yates correction.
Fisher's exact test.

Table 3. Comparison of symptoms among patients with oral lichen planus (OLP) treated with systemic plus topical and topical therapy after 2 and
6 months of treatment

Clinical response

After 2 months of treatment After 6 months of treatment

Group No symptoms Symptoms No symptoms Symptoms

Test (n 22) 16 (72.7%) 6 (27.3%) 18 (81.8%) 4 (18.2%)
Controly (n 23) 15 (65.2%) 8 (34.8%) 19 (82.6%) 4 (17.4%)
P 0.82z 0.82z 1.0 1.0

Treated with prednisone plus clobetasol.
yTreated with clobetasol.
zChi-square with Yates correction.
Fisher's exact test.

Fig. 1. Patients no. 13, systemic and topical treatment with atrophicerosive oral lichen planus (OLP; a, b). The same patient after 6 months of systemic,
topical, and antimicotic treatment (c, d). Partial response.

326 J Oral Pathol Med 32: 3239


Fig. 2. Patient no. 7, topical treatment with atrophicerosive oral lichen planus (OLP; a, b). The same patient after 6 months of therapy with clobetasol
propionate ointment and antimicotic treatment (c, d). Complete response.
systemic side-effects (such as blood pressure increase, four
patients (two in the rst, one in the third, and one in the fourth
week of treatment); epigastric pain, three patients (all in the rst
week), and water retention, two patients (in the third and fourth
week), whereas none of the control-group patients contracted
systemic side-effects (P 0.003, Fisher's exact test).
Discussion
There are contrasting opinions about mainstay treatment of
patients with OLP: some authors consider systemic corticosteroid
therapy the most effective, whereas others advocate the topical
use of very high potency corticosteroids (14). Whereas some
double-blind placebo-controlled studies (57, 1517) have shown
that topical steroid agents such as uocinonide and clobetasol are
safe and effective in the treatment of OLP, the literature on
systemic steroid use in OLP is limited to open clinical studies
(11, 14, 22).
Unfortunately, meta-analysis of the published data is difcult,
given the great heterogeneity of the reports and the rarity of the
Corticosteroid treatment of oral lichen planus
studies comparing the effect of topical and systemic steroid
therapy. Moreover, there are few data on long-term therapeutic
outcome for OLP patients (1). Thus, there is no denitive treat-
ment that clearly results in long-term remission.
This study is apparently the rst directly comparing topical
and systemic corticosteroid therapy in OLP patients on long-term
follow-up. We used prednisone because it is the most used
systemic corticosteroids in OLP treatment, and its efcacy and
adverse side-effects are well known. Deazacort is reported to
produce less metabolic sequelae than prednisone, but it is less
potent and uncommonly used in the OLP treatment (19).
We choose to use quite a high dose (50 mg/day) not to
underestimate the effect of prednisone in OLP, but because of
the fact that others have also used or recommended doses up to
80 mg/day (4, 14). Nevertheless, our data did not reveal signi-
cant differences in response using systemic prednisone followed
by topical clobetasol propionate in adhesive base, or only topical
clobetasol. Indeed, 68.2% of the patients treated with systemic
plus topical corticosteroids and 69.6% of the topically treated
patients underwent complete remission. In agreement, a greater
level of symptom control was achieved with topical rather than
systemic corticosteroids or a combination of local and systemic
corticosteroids in only one published study (11), although no
J Oral Pathol Med 32: 3239 327
Carbone et al.
statistical comparison was made. Others reported a higher rate
(89100%) of efcacy with prednisone, but they also included
diseases other than OLP, such as recurrent aphthous stomatitis
and erythema multiforme, which usually show better response
with anti-inammatory therapy (14).
Moreover, we used an induction dose of prednisone lower than
others (50 mg/day vs. up to 60 mg/day) that could partially
account for the different results (14). However, adverse effects
of systemic corticosteroids therapy, which occurred in 32% of the
patients in our study, were clearly lower than those reported using
higher doses of prednisone (61% of cases) (12, 14).
The follow-up also showed similar outcomes for both the
treatments. After an average time of 3 years, 50% of the systemi-
cally plus topically treated group and 45% of the clobetasol-treated
group maintained improvement. Conversely, there was a notably
higher incidence of systemic side-effects in the prednisone-trea-
ted group, although in several cases, there was only a short-term
treatment. Almost one-third of the systemically treated patients
experienced adverse effects from hypertension to water retention,
whereas none of the topically treated patients referred systemic
side-effects. Although the adverse-effects were, in most cases,
mild and did not cause drop-out, their importance on the patient's
compliance could not be undervalued, also considering the
advanced age of most of the subjects.
In conclusion, this study suggests that topical high-potency
corticosteroids should be the mainstay treatment for most of the
patients with atrophicerosive OLP. In particular, clobetasol in
adhesive medium has proved to be safe and effective in control-
ling OLP, although half of the treated patients required subse-
quent treatment on long-term follow-up. Systemic corticosteroids
should probably be indicated at high dose (up to 1.52 mg/kg/
day) for a minority of patients with recalcitrant severe erosive or
atrophic OLP where topical approaches have failed, or for diffuse
mucocutaneous involvement such as vulvovaginal LP (23, 24).
However, new promising topical agents as tacrolimus could
obviate the need for systemic corticosteroids therapy also for
recalcitrant OLP cases (2527).
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